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1.
Proc Natl Acad Sci U S A ; 118(31)2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34282032

RESUMO

Changes in the distribution and abundance of invasive species can have far-reaching ecological consequences. Programs to control invaders are common but gauging the effectiveness of such programs using carefully controlled, large-scale field experiments is rare, especially at higher trophic levels. Experimental manipulations coupled with long-term demographic monitoring can reveal the mechanistic underpinnings of interspecific competition among apex predators and suggest mitigation options for invasive species. We used a large-scale before-after control-impact removal experiment to investigate the effects of an invasive competitor, the barred owl (Strix varia), on the population dynamics of an iconic old-forest native species, the northern spotted owl (Strix occidentalis caurina). Removal of barred owls had a strong, positive effect on survival of sympatric spotted owls and a weaker but positive effect on spotted owl dispersal and recruitment. After removals, the estimated mean annual rate of population change for spotted owls stabilized in areas with removals (0.2% decline per year), but continued to decline sharply in areas without removals (12.1% decline per year). The results demonstrated that the most substantial changes in population dynamics of northern spotted owls over the past two decades were associated with the invasion, population expansion, and subsequent removal of barred owls. Our study provides experimental evidence of the demographic consequences of competitive release, where a threatened avian predator was freed from restrictions imposed on its population dynamics with the removal of a competitively dominant invasive species.


Assuntos
Distribuição Animal , Espécies Introduzidas , Estrigiformes/fisiologia , Animais , Ecossistema , Noroeste dos Estados Unidos , Dinâmica Populacional
2.
Comp Med ; 71(2): 177-187, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33579397

RESUMO

Aging of the immune system is characterized by the loss of naïve T-cells, increased inflammation, and immune function impairment. Chronic infection with cytomegalovirus is thought to play a role in age-related changes in immunity. Therefore, to assess the effect of pathogens such as cytomegalovirus on the immune system, we determined lymphocyte populations and inflammatory markers over a 3-y period in captive, middle-age baboons, with various exposure to pathogens and shedding pressure. Groups included SPF (i.e., pathogen-negative; n = 14); large-group, conventionally housed (CONV LG; pathogen- positive; n = 14), and small-group, conventionally housed (CONV SM; pathogen-positive; n = 7). All baboon groups showed a decrease in CD45RA+ CD28+ (i.e., naive) cells over time during middle age, but the rate of decline appeared faster in CONV LG baboons than in the other groups. In addition, the reduction in CD45RA+ CD28+ cells in the CONV LG baboons coincided with higher IgG levels against baboon cytomegalovirus, increased serum cortisol concentration, and a greater inflammatory phenotype. The results of this project support a role for cytomegalovirus infection in immune system alterations in middle-aged baboons.


Assuntos
Infecções por Citomegalovirus , Papio anubis , Envelhecimento , Animais , Papio , Linfócitos T
3.
Int J Pediatr Otorhinolaryngol ; 138: 110368, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152962

RESUMO

OBJECTIVE: To evaluate which factors may affect anxiety and child's health perception of parents with children that have laryngomalacia. STUDY DESIGN: Survey Study. SETTING: "Coping with Laryngomalacia" - largest online laryngomalacia support group for parents with children who have laryngomalacia. SUBJECTS: and Methods: A survey was sent to support group member that gathered information regarding the patient's diagnosis and associated course of treatment and evaluated for parental anxiety and perceived health of their child. Analysis was performed to evaluate which variables are associated with increased parental anxiety and worsened perceived child's health. RESULTS: Data was gathered on 434 patients. All caregivers reported some level of anxiety due to the diagnosis and 64% felt completely anxious. Parents who saw an increased number of physicians prior to a pediatric ENT rated their child with poorer health (p < .05). Those that felt their concerns were brushed off initially reported increased anxiety (p < .05). If the child was admitted to the hospital, ICU, required intubation, had feeding troubles, required a feeding tube, or underwent pH monitoring, the patient was rated to have poorer health per the parents (p < .05). CONCLUSION: Laryngomalacia causes a significant burden on patients and their families due to the eating problems, feeding problems, hospital stay, and other various conditions associated with the disease. Caregivers should take a more modern and compassionate approach to management and diagnosis.


Assuntos
Cuidadores/psicologia , Efeitos Psicossociais da Doença , Laringomalácia , Grupos de Autoajuda , Ansiedade , Criança , Humanos , Laringomalácia/diagnóstico , Laringomalácia/terapia , Pais , Inquéritos e Questionários
4.
Biometrics ; 75(3): 799-809, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31004437

RESUMO

Over the past decade, there has been much methodological development for the estimation of abundance and related demographic parameters using mark-resight data. Often viewed as a less-invasive and less-expensive alternative to conventional mark recapture, mark-resight methods jointly model marked individual encounters and counts of unmarked individuals, and recent extensions accommodate common challenges associated with imperfect detection. When these challenges include both individual detection heterogeneity and an unknown marked sample size, we demonstrate several deficiencies associated with the most widely used mark-resight models currently implemented in the popular capture-recapture freeware Program MARK. We propose a composite likelihood solution based on a zero-inflated Poisson log-normal model and find the performance of this new estimator to be superior in terms of bias and confidence interval coverage. Under Pollock's robust design, we also extend the models to accommodate individual-level random effects across sampling occasions as a potentially more realistic alternative to models that assume independence. As a motivating example, we revisit a previous analysis of mark-resight data for the New Zealand Robin (Petroica australis) and compare inferences from the proposed estimators. For the all-too-common situation where encounter rates are low, individual detection heterogeneity is non-negligible, and the number of marked individuals is unknown, we recommend practitioners use the zero-inflated Poisson log-normal mark-resight estimator as now implemented in Program MARK.


Assuntos
Demografia/estatística & dados numéricos , Modelos Biológicos , Modelos Estatísticos , Animais , Densidade Demográfica , Tamanho da Amostra , Aves Canoras
5.
Am J Vet Res ; 80(3): 294-299, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30801213

RESUMO

OBJECTIVE To evaluate the effectiveness and safety of dipyrone to control pyrexia in horses with naturally occurring disease under field conditions. ANIMALS 138 horses with pyrexia and various infections evaluated at 14 veterinary sites in 12 states. PROCEDURES In the first (effectiveness) phase of this 2-phase study, horses were randomly assigned 3:1 to receive 1 dose of dipyrone (30 mg/kg [13.6 mg/lb], IV) or an equivalent amount of placebo. Effectiveness was defined as a decrease in rectal temperature ≥ 1.1°C (2°F), compared with the pretreatment value, or a rectal temperature of ≤ 38.3°C (101.0°F) 6 hours after treatment administration. Horses deemed to have an appropriate reduction in rectal temperature (regardless of treatment group) by 6 hours were immediately entered into the safety phase of the study, in which dipyrone was administered IV at 30 mg/kg between 0 and 8 times up to every 8 hours on an as-needed basis, as determined by the clinical investigators. Horses were monitored throughout for adverse events. RESULTS A significantly greater proportion of dipyrone-treated horses (76/99 [77%]) had an effective treatment response than did placebo-treated horses (6/31 [19%]). Posttreatment adverse events were mild and transient. No differences in types or prevalence of gastrointestinal adverse events were evident between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE Dipyrone was effective in controlling pyrexia by 6 hours after IV administration of a single 30-mg/kg dose in a large proportion of treated horses. Adverse effects were minimal.


Assuntos
Antipiréticos/uso terapêutico , Dipirona/uso terapêutico , Febre/veterinária , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Dipirona/administração & dosagem , Feminino , Febre/tratamento farmacológico , Cavalos , Masculino , Distribuição Aleatória , Fatores de Tempo , Resultado do Tratamento
6.
Comp Med ; 69(1): 55-62, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30704552

RESUMO

Cytomegalovirus (CMV) is a common chronic herpesvirus found in humans and numerous other mammalian species. In people, chronic viruses like CMV can alter overall health and immunity and pose a serious risk for those with an inadequate immune system. In addition, CMV plays an important role in animal health, and could affect the health of vulnerable populations, like endangered species. Previous studies found a high rate of CMV seropositivity among adult baboons (Papio anubis), and results from our laboratory revealed that baboon CMV (BaCMV) seropositivity was correlated with altered immune cell populations. In the current study, we further characterized BaCMV infection in normal, adult baboons. Analysis of blood samples from baboons (age, 6 to 26 y) revealed a low overall prevalence of detectable of BaCMV DNA, with a higher detection rate in aged baboons (older than 15 y). Furthermore, data suggest that individual baboons maintain similar rates of recurrence and levels of BaCMV shedding in saliva over time. Finally, we evaluated multiple commercially available assays for antihuman CMV IgG and IgM for use with baboon sera. Results of this study will improve our understanding of BaCMV and may be directly relevant to other closely related species.


Assuntos
Infecções por Citomegalovirus/veterinária , Doenças dos Macacos/patologia , Papio anubis , Fatores Etários , Animais , Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/patologia , DNA Viral/sangue , Doenças dos Macacos/sangue , Doenças dos Macacos/imunologia , Saliva/virologia , Eliminação de Partículas Virais
7.
J Am Assoc Lab Anim Sci ; 56(1): 52-56, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-28905715

RESUMO

In this study, we evaluated the efficacy of combined treatment with ivermectin and fenbendazole (IVM-FBZ) for treating captive olive baboons (Papio anubis) infected with Strongyloides fülleborni and Trichuris trichiura, 2 common nematode parasites of these NHP. Infected baboons were treated for a total of 9 wk with ivermectin (400 µg/kg IM twice weekly) and fenbendazole (50 mg/kg PO once daily for 3 d; 3 rounds of treatment, 21 d apart). Five baboons naturally infected with both S. fülleborni and T. trichiura (n = 4) or S. fülleborni alone (n = 1) received the combination therapy; an additional baboon infected with both parasites served as a nontreated control. The efficacy of IVM-FBZ was measured as the reduction in fecal egg counts of S. fülleborni and T. trichiura as determined by quantitative fecal flotation examination after treatment of baboons with IVM-FBZ. All baboons treated with IVM-FBZ stopped shedding S. fülleborni and T. trichiura eggs by 8 d after treatment and remained negative for at least 161 d. The nontreated control baboon shed S. fülleborni and T. trichiura eggs throughout the study period. Our results indicate that the IVM-FBZ regimen was efficacious for treating olive baboons infected with S. fülleborni and T. trichiura.


Assuntos
Fenbendazol/uso terapêutico , Ivermectina/uso terapêutico , Doenças dos Macacos/parasitologia , Papio anubis , Strongyloides , Trichuris , Animais , Animais de Laboratório , Coinfecção , Fezes/parasitologia , Feminino , Fenbendazol/administração & dosagem , Ivermectina/administração & dosagem , Masculino , Doenças dos Macacos/tratamento farmacológico , Projetos Piloto , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/veterinária , Tricuríase/tratamento farmacológico , Tricuríase/veterinária
8.
Blood Cells Mol Dis ; 63: 1-8, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27888688

RESUMO

An oral therapeutic which reduces duration of cytopenias and is active following accidental radiation exposures is an unmet need in radiation countermeasures. Alpha methylhydrocinnamate (ST7) prolongs STAT-5 phosphorylation, reduces growth-factor dependency of multi-lineage cell lines, and stimulates erythropoiesis. Here, ST7 and its isomers were studied for their effects on myeloid progenitors and hematopoietic stem cells (HSCs) following radiation, in nonhuman primates, and murine irradiation models. Addition of ST7 or ST7-S increased CFU-GM production by 1.7-fold (p<0.001), reduced neutrophil apoptosis comparable to G-CSF, and enhanced HSC survival post-radiation by 2-fold, (p=0.028). ST7 and ST7-S administered in normal baboons increased ANC and platelet counts by 50-400%. In sub-lethally-irradiated mice, ANC nadir remained >200/mm3 and neutropenia recovered in 6days with ST7 treatment and 18days in controls (p<0.05). In lethally-irradiated mice, marrow pathology at 15days was hypocellular (10% cellularity) in controls, but normal (55-75% cellularity) with complete neutrophil maturation with ST7-S treatment. Following lethal irradiation, ST7, given orally for 4days, reduced mortality, with 30% survival in ST7-animals vs 8% in controls, (p<0.05). Collectively, the studies indicate that ST7 and ST7-S enhance myeloid recovery post-radiation and merit further evaluation to accelerate hematologic recovery in conditions of radiation-related and other marrow hypoplasias.


Assuntos
Células Mieloides/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Fenilpropionatos/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Irradiação Corporal Total/efeitos adversos , Animais , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos da radiação , Camundongos , Células Mieloides/efeitos da radiação , Neutrófilos/efeitos da radiação , Papio , Fenilpropionatos/farmacologia , Exposição à Radiação/efeitos adversos , Taxa de Sobrevida , Irradiação Corporal Total/mortalidade
9.
PLoS One ; 10(12): e0145305, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26694648

RESUMO

A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE) cells in eyes affected by Stargardt's disease, age-related macular degeneration (AMD), and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN) inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs) such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP) administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG) and histological analysis showed that rats treated with PBNDs retained ~90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75-80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control). In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE) by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat retina from light damage. There is potential in developing these compounds as preventative therapeutics for the treatment of human retinal degenerations in which the accumulation of lipofuscin may be pathogenic.


Assuntos
Óxidos N-Cíclicos/administração & dosagem , Luz/efeitos adversos , Doenças Retinianas/prevenção & controle , Epitélio Pigmentado da Retina/efeitos dos fármacos , Rodopsina/metabolismo , Animais , Bovinos , Óxidos N-Cíclicos/química , Óxidos N-Cíclicos/farmacologia , Feminino , Injeções Intraperitoneais , Masculino , Camundongos , Papio anubis , Ratos , Doenças Retinianas/etiologia , Doenças Retinianas/metabolismo , Epitélio Pigmentado da Retina/efeitos da radiação , cis-trans-Isomerases/antagonistas & inibidores , cis-trans-Isomerases/metabolismo
10.
PLoS One ; 10(12): e0144660, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26713848

RESUMO

High-level fetal (γ) globin expression ameliorates clinical severity of the beta (ß) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies.


Assuntos
Anemia/genética , Hemoglobina Fetal/genética , Ensaios de Triagem em Larga Escala , Papio , Ativação Transcricional/efeitos dos fármacos , gama-Globinas/genética , Animais , Benserazida/efeitos adversos , Benserazida/farmacologia , Avaliação Pré-Clínica de Medicamentos , Células Precursoras Eritroides/efeitos dos fármacos , Loratadina/efeitos adversos , Loratadina/análogos & derivados , Loratadina/farmacologia , Camundongos , Camundongos Transgênicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
11.
PLoS One ; 9(9): e107167, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25244034

RESUMO

The human immune system undergoes age-related changes that can lead to increased disease susceptibility. Using the baboon as a model for human immune system aging, we examined age-related changes in relative and absolute numbers of T cell subpopulations, cytomegalovirus (CMV) titer and markers of inflammation. In addition, the effect of gender, social status and peer group on lymphocyte subpopulations was determined. Relative and absolute numbers of total lymphocytes (CD3+), T helper cells (CD4+), and cytotoxic T cells (CD8+) increased with age. The proportion of naïve T cells (CD45RA+) decreased, while the total number of cells negative for the co-stimulatory receptor, CD28 (CD28-) increased in an age-dependent manner. Furthermore, CMV titers were negatively correlated with the number of naive CD4+ cells. IL-6 and cortisol concentration were also negatively associated with T cell subpopulations. Additionally, socially dominant baboons exhibited decreases in naïve CD4+ and CD8+ cells (by 65% and 52%, respectively) compared to subordinate animals. These results suggest that factors such as CMV exposure and inflammation may contribute to the age-related decline in immune health and indicate that factors like social status should be considered when studying immunosenescence in animal models.


Assuntos
Envelhecimento/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus , Inflamação/imunologia , Subpopulações de Linfócitos T/imunologia , Fatores Etários , Envelhecimento/sangue , Envelhecimento/patologia , Animais , Biomarcadores/sangue , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/patologia , Hidrocortisona/sangue , Sistema Imunitário/imunologia , Sistema Imunitário/patologia , Inflamação/sangue , Inflamação/patologia , Interleucina-6/sangue , Papio , Subpopulações de Linfócitos T/patologia
12.
PLoS One ; 9(4): e95900, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24780906

RESUMO

Age-related macular degeneration (AMD) is a common yet complex retinal degeneration that causes irreversible central blindness in the elderly. Pathology is widely believed to follow loss of retinal pigment epithelium (RPE) and photoreceptor degeneration. Here we report aberrant expression of interleukin-17A (IL17A) and the receptor IL17RC in the macula of AMD patients. In vitro, IL17A induces RPE cell death characterized by the accumulation of cytoplasmic lipids and autophagosomes with subsequent activation of pro-apoptotic Caspase-3 and Caspase-9. This pathology is reduced by siRNA knockdown of IL17RC. IL17-dependent retinal degeneration in a mouse model of focal retinal degeneration can be prevented by gene therapy with adeno-associated virus vector encoding soluble IL17 receptor. This intervention rescues RPE and photoreceptors in a MAPK-dependent process. The IL17 pathway plays a key role in RPE and photoreceptor degeneration and could hold therapeutic potential in AMD.


Assuntos
Citocinas/antagonistas & inibidores , Interleucina-17/toxicidade , Degeneração Macular/prevenção & controle , Receptores de Interleucina-17/genética , Retina/efeitos dos fármacos , Transfecção , Dependovirus/genética , Vetores Genéticos , Humanos , Degeneração Macular/genética
13.
Parasitol Res ; 113(6): 2239-50, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24728521

RESUMO

Based on data obtained using vaccine efficacy studies in mice, hamsters, and baboons, the credentials of Sm-p80 as a first tier vaccine candidate for schistosomiasis have been well established. Sm-p80-based vaccine formulation(s) have consistently exhibited potent prophylactic efficacy in reducing adult worm burden following cercarial challenge and induce killing of established adult worms in chronic infection. This vaccine is protective against both intestinal and urinary schistosomiasis. In this study, the longevity of Sm-p80-specific antibody responses was studied in mice and in baboons. Robust antibody titers were detected in mice for up to 60 weeks following vaccination with Sm-p80 recombinant vaccine (Sm-p80 + GLA-SE). In the follow-up experiments to our published studies, Sm-p80-specific IgG was also detected in baboons 5-8 years following the initial vaccination with an Sm-p80 DNA vaccine. In one baboon, transfer of Sm-p80-specific antibody was detected in umbilical cord blood and in the baby. These long-lasting humoral immune response data coupled with the vaccine efficacy data in rodents and nonhuman primates further strengthens the case for Sm-p80 to be moved forward through development leading to human clinical trials.


Assuntos
Anticorpos Anti-Helmínticos/sangue , Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Vacinas/imunologia , Animais , Antígenos de Helmintos/imunologia , Biomphalaria/parasitologia , Cricetinae , Feminino , Sangue Fetal/química , Sangue Fetal/imunologia , Imunidade Materno-Adquirida , Imunoglobulina G/sangue , Camundongos , Papio , Gravidez , Schistosoma mansoni/genética , Vacinação , Vacinas de DNA/imunologia
14.
Xenotransplantation ; 21(3): 287-90, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24547993

RESUMO

Baboons have natural antibodies against pig antigens. We have investigated whether there are differences in anti-non-Gal pig antibody levels between baboons maintained under specific pathogen-free (SPF) conditions and those housed under conventional conditions (non-SPF) that might be associated with improved outcome after pig-to-baboon organ transplantation. Baboons (n = 40) were housed indoors (SPF n = 8) or in indoor/outdoor pens (non-SPF n = 32) in colonies of similar size and structure. Non-SPF colonies harbor a number of pathogens common to non-human primate species, whereas many of these pathogens have been eliminated from the SPF colony. Complete blood cell counts (CBC), blood chemistry, and anti-non-Gal IgM and IgG levels were monitored. There were no significant differences in CBC or blood chemistry between SPF and non-SPF baboons. Anti-non-Gal IgM levels were significantly lower in the SPF baboons than in the non-SPF baboons (MFI 7.1 vs. 8.8, P < 0.05). One SPF and two non-SPF baboons had an MFI >20; if these three baboons are omitted, the mean MFIs were 4.8 (SPF) vs. 7.5 (non-SPF) (P < 0.05). Anti-non-Gal IgG was minimal in both groups (MFI 1.0 vs. 1.0). As their levels of anti-non-Gal IgM are lower, baboons maintained under SPF conditions may be beneficial for xenotransplantation studies as the initial binding of anti-pig IgM to an α1,3-galactosyltransferase gene-knockout pig organ may be less, thus resulting in less complement and/or endothelial cell activation. However, even under identical SPF conditions, an occasional baboon will express a high level of anti-non-Gal IgM, the reason for which remains uncertain.


Assuntos
Anticorpos Heterófilos/metabolismo , Modelos Animais , Papio , Organismos Livres de Patógenos Específicos , Suínos , Transplante Heterólogo , Animais , Biomarcadores/metabolismo , Feminino , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Masculino , Papio/imunologia , Papio/metabolismo , Papio/cirurgia , Suínos/imunologia , Suínos/cirurgia
15.
Vaccine ; 32(11): 1296-303, 2014 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-24397898

RESUMO

The ability of the Schistosoma mansoni antigen, Sm-p80, to provide cross-species protection against Schistosoma haematobium challenge was evaluated in hamster and baboon models. Pronounced reduction in worm burden (48%) and in tissue egg load (64%) was observed in hamsters vaccinated with recombinant Sm-p80 admixed with glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE). Similarly, in baboons, the Sm-p80/GLA-SE vaccine produced a 25% reduction in S. haematobium adult worms and decreased the egg load in the urinary bladder by 64%. A 40% and 53% reduction in fecal and urine egg output, respectively, was observed in vaccinated baboons. A balanced pro-inflammatory (Th17 and Th1) and Th2 type of response was generated after vaccination and appears indicative of augmented prophylactic efficacy. These data on cross-species protection coupled with the prophylactic, therapeutic and antifecundity efficacy against the homologous parasite, S. mansoni, reinforces Sm-p80 as a promising vaccine candidate. It is currently being prepared for GMP-compliant manufacture and for further pre-clinical development leading to human clinical trials. These results solidify the expectation that the Sm-p80 vaccine will provide relief for both the intestinal and the urinary schistosomiasis and thus will be greatly beneficial in reducing the overall burden of schistosomiasis.


Assuntos
Proteção Cruzada , Schistosoma haematobium/patogenicidade , Schistosoma mansoni/imunologia , Esquistossomose/prevenção & controle , Vacinas/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Formação de Anticorpos , Antígenos de Helmintos/imunologia , Cricetinae , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Imunidade Celular , Masculino , Papio , Contagem de Ovos de Parasitas , Projetos Piloto , Vacinas Sintéticas/imunologia
16.
J Infect Dis ; 209(12): 1929-40, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24436452

RESUMO

No vaccines are available for human use for any parasitic infections, including the helminthic disease schistosomiasis. Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading antigen candidate for a schistosomiasis vaccine. Prophylactic and antifecundity efficacies of Sm-p80 have been tested using a variety of vaccine approaches in both rodent and nonhuman primate models. However, the therapeutic efficacy of a Sm-p80-based vaccine had not been determined. In this study, we evaluated the therapeutic efficacy of Sm-p80 by using 2 different strategies and 3 Sm-p80-based vaccine formulations in baboons. Vaccine formulations were able to decrease established adult worms by 10%-36%, reduce retention of eggs in tissues by 10%-57%, and decrease egg excretion in feces by 13%-33%, compared with control formulations. Marked differences were observed in B and T cell immune correlates between vaccinated and control animals. This is the first report of killing of established adult schistosome worms by a vaccine. In addition to distinct prophylactic efficacy of Sm-p80, this study adds to the evidence that Sm-p80 is a potentially important antigen with both substantial prophylactic and therapeutic efficacies. These data reinforce that Sm-p80 should be moved forward along the path toward human clinical trials.


Assuntos
Antígenos de Helmintos/imunologia , Calpaína/imunologia , Papio/parasitologia , Esquistossomose mansoni/tratamento farmacológico , Vacinas/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Anticorpos Anti-Helmínticos/imunologia , Linfócitos B/imunologia , Modelos Animais de Doenças , Fezes/parasitologia , Feminino , Interferon gama/sangue , Interleucina-17/sangue , Interleucina-4/sangue , Leucócitos Mononucleares/imunologia , Masculino , Contagem de Ovos de Parasitas , Schistosoma mansoni/efeitos dos fármacos , Linfócitos T/imunologia , Vacinação
17.
Ecol Evol ; 3(12): 4215-20, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24324871

RESUMO

In capture-recapture studies, the estimation accuracy of demographic parameters is essential to the efficacy of management of hunted animal populations. Dead recovery models based upon the reporting of rings or bands are often used for estimating survival of waterfowl and other harvested species. However, distance from the ringing site or condition of the bird may introduce substantial individual heterogeneity in the conditional band reporting rates (r), which could cause bias in estimated survival rates (S) or suggest nonexistent individual heterogeneity in S. To explore these hypotheses, we ran two sets of simulations (n = 1000) in MARK using Seber's dead recovery model, allowing time variation on both S and r. This included a series of heterogeneity models, allowing substantial variation on logit(r), and control models with no heterogeneity. We conducted simulations using two different values of S: S = 0.60, which would be typical of dabbling ducks such as mallards (Anas platyrhynchos), and S = 0.80, which would be more typical of sea ducks or geese. We chose a mean reporting rate on the logit scale of -1.9459 with SD = 1.5 for the heterogeneity models (producing a back-transformed mean of 0.196 with SD = 0.196, median = 0.125) and a constant reporting rate for the control models of 0.196. Within these sets of simulations, estimation models where σS = 0 and σS > 0 (σS is SD of individual survival rates on the logit scale) were incorporated to investigate whether real heterogeneity in r would induce apparent individual heterogeneity in S. Models where σS = 0 were selected approximately 91% of the time over models where σS > 0. Simulation results showed < 0.05% relative bias in estimating survival rates except for models estimating σS > 0 when true S = 0.8, where relative bias was a modest 0.5%. These results indicate that considerable variation in reporting rates does not cause major bias in estimated survival rates of waterfowl, further highlighting the robust nature of dead recovery models that are being used for the management of harvested species.

18.
CBE Life Sci Educ ; 12(2): 120-3, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23737615

RESUMO

This is an exciting time to be a biologist. The advances in our field and the many opportunities to expand our horizons through interaction with other disciplines are intellectually stimulating. This is as true for people tasked with helping the field move forward through support of research and education projects that serve the nation's needs as for those carrying out that research and educating the next generation of biologists. So, it is a pleasure to contribute to this edition of CBE-Life Sciences Education. This column will cover three aspects of the interactions of physics and biology as seen from the viewpoint of four members of the Division of Undergraduate Education of the National Science Foundation. The first section places the material to follow in context. The second reviews some of the many interdisciplinary physics-biology projects we support. The third highlights mechanisms available for supporting new physics-biology undergraduate education projects based on ideas that arise, focusing on those needing and warranting outside support to come to fruition.


Assuntos
Biologia/educação , Física/educação , Estudantes , Biologia/economia , Humanos , Física/economia , Universidades/economia
20.
Comp Med ; 63(3): 288-94, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23759532

RESUMO

Two young female baboons naturally infected with simian T-lymphotropic virus type 1 (STLV1) were euthanized due to chronic respiratory disease that was unresponsive to treatment. Massive lymphocytic infiltration of the lung interstitium suggested a diagnosis of STLV-associated lymphoma. In each case, the diagnosis was confirmed through inverse PCR (IPCR) that detected monoclonally integrated STLV1 provirus in cellular DNA extracted from lymphoma tissue and peripheral blood cells (PBC). One dominant STLV1-infected T-cell clone and 3 minor clones were detected in PBC from each baboon. Using archived PBC DNA and primers within the proviral genome and chromosomal DNA flanking the STLV1 integration sites in PCR analyses, we determined that the dominant clone in one baboon had first appeared approximately 8 mo after infection and had circulated for 4 y before clinical disease developed. ELISA testing of archived serum revealed that both baboons seroconverted to the p19 and p24 gag proteins and the envelope gp46 protein but not to the viral tax protein. Titers to p24 and gp46 rose significantly after infection and remained relatively constant until death, whereas titers to p19 increased with time. Although spontaneous STLV1-associated lymphomas have been described in baboons, the STLV1-associated lymphomas described here occurred in 2 relatively young baboons, both of whom had become infected with STLV at 3 to 4 y of age and developed lymphoma within 5 y of infection.


Assuntos
Linfoma/virologia , Vírus Linfotrópico T Tipo 1 de Símios/patogenicidade , Animais , Sequência de Bases , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Feminino , Genes Virais , Linfoma/imunologia , Papio , Reação em Cadeia da Polimerase/métodos , Vírus Linfotrópico T Tipo 1 de Símios/genética , Vírus Linfotrópico T Tipo 1 de Símios/isolamento & purificação , Carga Viral
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